Eukaryotic cell cycles seem to be controlled by a mysterious "commitment" event. In the yeast Saccharomyces cerevisiae, genes affecting the commitment event have been identified. Some of these genes, the Start genes, are required for commitment to occur, and other genes, the Whi genes, help determine when commitment will occur. The behaviour of at least one of the Whi mutants is consistent with the idea that the concentration of the gene product changes through the cell cycle, and at a critical concentration, commitment to a new cycle, and at a critical concentration, commitment to a new cell cycle is triggered. That is, the Whi gene product may be the metric that directly triggers commitment. The aim of this project is to characterize the Whi genes at the molecular level. Presently known Whi genes will be cloned, sequenced, mutated, and otherwise characterized. New Whi genes and interacting genes will be identified, and similarly characterized. Physiological studies of Whi mutants and some Start mutants will be undertaken, and the Whi gene products will be characterized biochemically, in an effort to determine the molecular nature of the commitment event. Through suppressor studies, an attempt will be made to identify Start genes that directly interact with Whi genes. Other eukaryotes will be screened for proteins antigenically related to the Whi proteins, in order to determine how generally applicable the mechanisms of yeast cell cycle control may be.